SUMMARY/ABSTRACT There has been unprecedented rise in the prevalence of stroke in sub-Saharan Africa (SSA), which when compared to stroke profiles in high-income countries (HIC) is characterized by a younger age of onset, higher case fatality rates, and more severe disability among survivors. Stroke survivors in SSA (vs. HIC) are especially at high risk for recurrent vascular events or death due to undiagnosed or under-controlled vascular risk factors, logistical challenges, low health literacy, and lack of care affordability. While international expert consensus secondary prevention guidelines recommend that antihypertensive, statin and anti-platelet therapy, be initiated promptly after ischemic stroke and adhered to in a persistent fashion to achieve optimal vascular risk reduction, these goals are seldom realized in routine clinical care settings in SSA. A relatively simple, low-cost, evidence- based strategy that could be largely applied in a uniform manner to stroke survivors in low- to ?middle income countries (LMICs), including the nations of SSA, is sorely needed. Fixed-dose combination pills, also known as ?polypills?, containing generic drugs, i.e. Aspirin, a statin, and blood pressure (BP) lowering medication(s) may be a viable avenue to improve medication adherence and consequently reduce risk of further disability or death on a large scale among stroke survivors encountered in resource-constrained regions. The overarching objective of the Stroke Minimization through Additive Anti-atherosclerotic Agents in Routine Treatment (SMAART) trial is to determine the preliminary impact of a polypill (Polycap DS ) containing fixed doses of antihypertensives, a statin, and antiplatelet therapy taken once daily orally in reducing future vascular risk compared to usual care in 120 recent stroke patients seen at a hospital in Kumasi, Ghana, while preparing for a future large, multicenter pragmatic trial and building local research capacity. In SMAART, we will 1) evaluate whether a polypill-based treatment strategy would result in carotid intimal media thickness stabilization/regression compared with usual care among recent stroke patients at one year after an index ischemic stroke; 2) assess whether a polypill-based treatment strategy improves vascular risk reduction drug adherence and tolerability, as well as blood pressure and serum holesterol control targets, compared with usual care among recent stroke patients at one year after an index ischemic stroke; and 3) provide increased capacity for conducting clinical research and continuous mentorship to early stage career investigators in Ghana, and facilitate their transition to independent investigators capable of planning and executing rigorous randomized controlled for secondary stroke prevention and vascular risk reduction in a resource-limited setting. A preliminarily feasible and efficacy-suggesting SMAART trial will inform the design of a future multi-center, double-blinded, placebo-controlled, randomized trial comparing the clinical efficacy of the polypill strategy vs ?usual care? in the African context to derive locally relevant, high-quality evidence for routine deployment of the polypill strategy for vascular risk moderation among stroke survivors in LMICs.